Under the influence of artists such as Little Richard, Elvis Presley, Chuck Berry and Otis Redding, McCafferty became one of the founding members of Nazareth in 1968. He has appeared on all of Nazareth's albums and has toured with them for 45 years. He co-wrote some of the big Nazareth hits, including "Broken Down Angel", "Dream On" and "Bad Bad Boy". He has released two solo albums. He is married and has two children.
On 29 August 2013, Nazareth announced Dan McCafferty's retirement from touring with the band due to health issues.
McCafferty elaborated on the specifics of the health issues and the state of his situation in an interview with the UK music magazine, Classic Rock. He stated that he had not suffered a stroke as had been reported in the press. He said that his chronic obstructive pulmonary disease (COPD) that has "worsened in recent years" had made him leave the stage in Switzerland in late August 2013 after only three songs, indicating that, "You don’t know when it's going to come on, but suddenly you can't breathe." Commenting about his most recent episode, at the Swiss festival, McCafferty maintained, "if you can't do the job you shouldn't be there — Nazareth's too big for that." McCafferty also revealed that another health problem was responsible for his onstage collapse at a concert in Canada in July 2013 — a burst stomach ulcer. He stated reflecting back on the incident, "I thought I'd be fine, but you lose so much blood when that happens." McCafferty also said he expects Nazareth to continue on without him. "I really hope they get someone else," he declared. "I'm sure they will." Although McCafferty is retiring from performing, Nazareth fans can still hear his voice on their 2014 album Rock 'n' Roll Telephone. The singer also revealed that he could record more new music, either with Nazareth or as a solo artist. He clarified: "To go into a studio and sing isn't like doing a gig. I could always make another record, but getting up to do an hour and three-quarters, and get people to pay money to come and see me — I can't do that." McCafferty expressed his appreciation to his fans near the end of the interview by saying: "Let everyone know I appreciate they've been there for all these years."